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In vitro and in vivo reconstruction of cutaneous stem cell system

皮肤干细胞系统的体外和体内重建

基本信息

批准号：
17390314
负责人：
OKOCHI Hitoshi
金额：
$ 9.35万
依托单位：
Research Institute, International Medical Center of Japan
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390314/
关键词：
keratinocytes dermal papilla cell hair follicle stem cell multipotency

项目摘要

We studied the outgrowth pattern of keratinocytes forming mono-layer sheet. We hypothesized that keratinocytes should balance the tension one another and we could prove it. After keratinocytes stratified, they stopped migrating and proliferating even if there was enough room for them. We demonstrated that keratinocytes produced unknown inhibitory molecules and secreted them in the culture medium. We performed mRNA analysis by differential display methods, but we have not identified the molecule yet.We focused on the dermal papilla cells because they are key players of hair follicle development. Recently, multipotent stem cells have been isolated from the skin and designated as skin-derived precursors (SKPs) that are localized in the dermal papilla of hair follicles. We found that CD133, a putative stem cell marker for hematopoietic cell, was expressed in the dermal papilla cells and was a novel cell surface marker for the DP cell. We could isolate the DP cells from embryonic and adult mice skin by using this marker and proved that CD133 positive cells had hair follicle-inducing ability. Moreover CD133 positive cells differentiated neuronal and mesodermal lineage cells. We also succeeded in culturing DP cells for a long time with keeping hair follicle-inducing ability. Furthermore we demonstrated that artificially aggregated DP cells promoted hair follicle induction when they were combined with epidermal cells in vivo. We noticed that when the hair follicle was reconstructed, sebaceous glands were accompanied at the same time. We also confirmed that cultured dermal papilla cells became dermal sheath cells as well as dermal papilla cells in vivo. Our observations imply that dermal papilla cells may rebuild their microenvironment and behave as both dermal papilla cells and dermal sheath cells as they adjust.

我们研究了角质形成细胞形成单层片的生长模式。我们假设角质形成细胞应该平衡彼此的张力，我们可以证明这一点，角质形成细胞分层后，即使有足够的空间，他们也停止迁移和增殖。我们证明，角质形成细胞产生未知的抑制分子，并分泌到培养基中。我们用差异显示方法进行mRNA分析，但我们还没有鉴定出这种分子。我们把重点放在毛乳头细胞上，因为它们是毛囊发育的关键参与者。最近，多能干细胞已经从皮肤中分离出来，并被称为皮肤来源的前体细胞（SKPs），其位于毛囊的真皮乳头中。我们发现，CD 133，一个假定的造血细胞的干细胞标志物，在毛乳头细胞中表达，是DP细胞的一个新的细胞表面标志物。利用该标记物，我们可以从胚胎和成年小鼠皮肤中分离出DP细胞，证明CD 133阳性细胞具有毛囊诱导能力。此外，CD133阳性细胞分化为神经元和中胚层谱系细胞。我们还成功地培养了DP细胞，并保持了毛囊诱导能力。此外，我们证明，人工聚集的DP细胞促进毛囊诱导时，他们与表皮细胞在体内结合。我们注意到毛囊重建的同时也伴随着皮脂腺的生成。我们还证实，培养的毛乳头细胞成为真皮鞘细胞以及毛乳头细胞在体内。我们的观察结果表明，毛乳头细胞可能会重建其微环境，并表现为毛乳头细胞和真皮鞘细胞，因为他们调整。